TGF-PI mRNA and protein were recently found to increase in animal brains after experimental lesions that cause local deafferentation or neuron death. Elevations of TGF-PI mRNA after lesions are prominent in microglia but are also observed in neurons and astrocytes. Moreover, TGF-PI mRNA autoinduces its own mRNA in the brain. These responses provide models for studying the increases of TGF-PI protein observed in PAiamyloid-containing extracellular plaques of Alzheimer's disease (AD) and Down's syndrome (DS) and in brain cells of AIDS victims.
Involvement of TGF-01 in these human brain disorders is discussed in relation to the potent effects of TGF-PI on wound healing and inflammatory responses in peripheral tissues.
We hypothesize that TGF-PI and possibly other TGF-P peptides have organizing roles in responses to neurodegeneration and brain injury that are similar to those observed in non-neural tissues. Work from many laboratories has shown that activities of TGF-P peptides on brain cells include chemotaxis, modification of extracellular matrix, and regulation of cytoskeletal gene expression and of neurotrophins. Similar activities of the TGF-P's are well established in other tissues.